The Mechanistic Roles Of Sialyltransferase ST6GAL1 In Fundamental Research And Clinical Application Of Colorectal Cancer

Colorectal cancer(CRC)is one of the most common malignancies in the world,with the third highest incidence but the second highest mortality rate.Tumor metastasis and recurrence are the main causes of death in CRC patients.Although surgical resection is an effective way to cope with lymph node metastasis,the extent of lymph node to be removed is in great dispute.As for distant metastasis,there hasn't been an effective way,so understanding the mechanism of CRC metastasis is of great significance to improve the prognosis of CRC patients.A common post-translational modification of sialylation,which belongs to terminal modification,is often present on the cell surface and participates in the identification,adhesion,and signal transmission between cells.The sialyltransferase ST6GAL1 specifically catalyzes the structure of a2,6 sialic acid,which has been reported to be associated with the progression of various tumors,but its specific mechanism remains unclarifiedFirstly,according to the previous findings of our group,ST6GAL1 may affect the metastasis of CRC.We established cell lines with overexpression/knockdown of ST6GAL1,and found over-expression of ST6GAL1 could inhibit the migratory ability while knock-down of it had opposite effect both in vivo and in vitro.Then the bio-informatics analysis reveal a positive correlation between ST6Gal-1 and ICAM-1 Moreover,the immunoblots showed ICAM-1 showed a declining trend from stage I and II CRC patients to stage ? and ? cases.And the results of lectin pulldown and protein stability showed ST6GAL1 overexpression could increase the protein expression by increasing the stability of ICAM-1 through sialylation,and ST6GAL1 knockdown had the opposite resultsSecondly,to explore the feasibility of ICAM-1 as a tumor marker,we examined the relationship between sialic acid levels of serum sICAM-1 and CRC staging,and found that the sialic acid level of sICAM-1 was also significantly lower than that of metastatic period,which can be used as a potential tumor markerIn summary,we used biochemistry,cell biology and other means to reveal the mechanism of ST6GAL1 regulate its substrate protein ICAM-1 sialylation and affect CRC metastasis.And we also proposed a new probable biomarker.